title: The density and type of MECA-79-positive high endothelial venules correlate with lymphocytic infiltration and tumour regression in primary cutaneous melanoma.
abstract: OBJECTIVE
  Tumour-infiltrating lymphocytes have prognostic value in malignant melanoma. High endothelial venules (HEVs) are specialized vessels present in lymph nodes and tertiary lymphoid organs. CCL19, CCL21 and CCR7 regulate lymphocyte migration through HEVs. The aim of our study was to correlate HEV density in cutaneous primary and metastatic malignant melanomas with clinicopathological parameters, and with CCL19, CCL21 and CCR7 mRNA expression.
  
  
  RESULTS
  High endothelial venule density was evaluated by immunohistochemistry with a specific antibody, MECA-79, and chemokine expression was evaluated by real-time PCR. MECA-79-positive vessels, covered by cuboidal (C-HEV) or flat (F-HEV) endothelium, were detected in 55% of melanomas. HEV density was higher in primary melanomas than in metastases. Positive correlations were found between C-HEV density and lymphocytic infiltration, and between F-HEV density and tumour regression. Cases in which the number of C-HEVs exceeded that of F-HEVs had higher levels of CCL19, CCL21, and CCR7.
  
  
  CONCLUSIONS
  Our results support a predominant role for C-HEV in the recruitment of lymphocytes in cutaneous melanomas, mediated by CCL19 and CCL21, whereas the density of F-HEV strongly correlates with tumour regression, Therefore, cuboidal and flat HEVs may serve as indicators of the active and late quiescent phases, respectively, of tumour regression in cutaneous malignant melanoma.
authors.affiliation: Department of Pathology, University of Valencia, Valencia, Spain; Department of Cellular and Molecular Biology, University of Medicine and Pharmacy, Craiova, Romania.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Avram
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sánchez-Sendra
authors.forename: José M
authors.initials: JM
authors.lastname: Martín
authors.forename: Liria
authors.initials: L
authors.lastname: Terrádez
authors.forename: David
authors.initials: D
authors.lastname: Ramos
authors.forename: Carlos
authors.initials: C
authors.lastname: Monteagudo
mesh_terms: D000954:Antigens, Surface / Q000378:metabolism*; D054415:Chemokine CCL19 / Q000235:genetics; D054421:Chemokine CCL21 / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042601:Lymphatic Vessels / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology*; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology*
chemical_list: D000954:Antigens, Surface; C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; C069886:L-selectin counter-receptors; D008565:Membrane Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D054400:Receptors, CCR7
keywords: CC-chemokine ligand 19; CC-chemokine ligand 21; MECA-79; chemokine CC-receptor 7; chemokines; high endothelial venules; melanoma; regression; tumour-infiltrating lymphocyte